This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Melanin is a key component of the human pigmentary system. The degree of pigmentation of the human skin, eyes or hair is to a large extent determined by the ability of cells to synthesize eumelanin and pheomelanin. The various functions of the melanins are defined by their chemical and physical properties. These properties in turn are defined by the molecular, supermolecular and aggregate-level structures. The ultimate goal is to construct a consistent model of these physical effects in order to engender understanding of how molecular and cellular scale structures relate to macroscopically observable properties and functions of melanins aiding the design of appropriate medical treatment modalities. Most natural melanin pigments exhibit a single, slightly asymmetric ESR signal at X-band that contains very little structural information. Preliminary W-band cw-ESR measurements of natural melanin granules, isolated from human retinal pigment epithelium, indicate distinct changes of the ESR spectrum that suggest possible age-dependent in situ photo oxidation of the ocular melanin. Our aim is to use even higher ESR frequencies/fields to spectrally resolve these small physicochemical changes of ocular melanin that may result from integrated exposure to light and oxidative stress. Our initial cw study is at 170/240 GHz concentrated on synthetic melanin (Sigma Aldrich). Notably, the major spectral features are very similar to that of humic acid. We found that the spectrum of the sodium salt of humic acid (Sigma-Aldrich) at 241 GHz/9T has to within experimental uncertainty the same linewidth and g-factor as observed for synthetic melanin. The interesting question is the origin of the subtle, narrow features contained in the broad single line of the synthetic melanin. Since melanins are known for their unusual electric conductivity behavior, it is possible that the presence of the narrow line in the spectrum of synthetic melanin demonstrates correlations between semiquinone radicals (abundant in melanin). Further multifrequency HFHF ESR, due to its superior g-factor resolution, and pulse ESR investigation will help to distinguish and separate between the two broad and narrow components of the spectrum and refine their interpretation.